[Protective effect of Chinese medicines on toxic side effects of cis-diamminedichloroplatinum in mice].
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Biomedical subjects
Publications and source records attributed to K Shibuya.
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The effect of ubenimex on the release of interleukin 1 (IL-1) and interleukin 2 (IL-2) from immuno-competent cells was studied. Ubenimex enhanced release of IL-1 from mouse peritoneal macrophages at 1.0 and 100 micrograms/ml in vitro and the release at 1.0 microgram/ml was larger. When ubenimex was administered to mice IL-1-releasing activity of the peritoneal macrophages was enhanced 3 and 5 days after the administration but not enhanced 1 day after the administration. Ubenimex also enhanced IL-2 release from rat spleen cells at 0.1 and 10 micrograms/ml, when concanavalin A (Con A) was added in the IL-2-releasing system. The enhancement was still observed with mouse spleen cells, when serum was further added. Moreover, thymocyte-proliferating activity was attained in the broths which rat spleen cells were incubated with ubenimex from 0.1 to 10 micrograms/ml in the absence and presence of Con A.
Recombinant erythropoietin (Epo) was capable of stimulating murine megakaryopoiesis both in serum-containing and serum-free cultures, although a relatively high amount of Epo was necessary to provide sufficient stimulus for colony growth. This observation was further confirmed by experiments using nonadherent, nonphagocytic, and T-cell-depleted marrow cells in which Epo stimulated the growth of single megakaryocytes, as well as clusters or colonies. Total plate analysis revealed that twice as many single megakaryocytes and two-cell aggregates were generated by Epo than generated by pokeweed mitogen-stimulated spleen cell-conditioned medium (PWM-SCM). The number of colonies with four or more cells formed by PWM-SCM, however, was significantly higher than that generated by Epo. These results suggest that in comparison to the factor(s) in PWM-SCM, Epo stimulates the growth of more mature progenitors.
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A case of a "so-called carcinosarcoma" of the pancreas that occurred in a 48-year-old female is reported. At autopsy, the pancreatic tumor was seen to have deeply invaded the gastric wall, causing ulceration. The pancreatic tumor consisted of two different histological components: a squamous cell carcinoma and spindle-cell sarcomatous tumor cells. Transitional areas between the two different tumor cells were also present. Since there were transitional areas and a lack of definitive electron microscopic evidence favoring a sarcoma in the sarcomatous tumor cells, the pancreatic tumor was considered to represent a "so-called carcinosarcoma".
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The effect of ubenimex on the progression of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced stomach tumor in rats was studied. Tumor induction was performed by giving MNNG via drinking water for 34 weeks. Ubenimex was ip administered twice a week at 0.5 mg/kg for 84 weeks in one group and 49 weeks in another starting from the first and 36th weeks after initiation of MNNG administration, respectively. The stomachs were endoscopically examined 2 times. At the 64th week after initiation of MNNG administration tumorous lesions were observed with about 70% of the rats in both ubenimex administration groups. In the ubenimex non-administration group nearly 90% of the rats had the lesions. After completion of ubenimex administration almost all the rats had the lesions in the three groups but the sizes were much smaller with the two ubenimex administration groups. Almost all of these lesions were histopathologically identified as tumorous. The tumor volume per rat in the two ubenimex administration groups from the 1 and 36th weeks was 21.0 and 19.2% of the volume in the control group, respectively. Tumor number per rat was similar among the three groups. The natural killer activity of rats was also examined after completion of the above experiment. The activity markedly increased when ubenimex was administered from the 36th week after initiation of MNNG administration. When ubenimex was administered from the first week, the activity did not increase demonstratively. From all the results described above we conclude that ubenimex exerts an inhibitory action against the progression of MNNG-induced stomach tumor in rats. Contribution of the increase of natural killer activity to ubenimex antitumor action may be dependent on schedule of ubenimex administration.
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In the rat, DNA carrying a cluster of the genes for tRNAAsp, tRNAGly, and tRNAGlu, aligned in that order, is repeated about 10 times. Seven DNA clones corresponding to the independent repeating units were isolated from a rat gene library. Nucleotide sequence analysis of these clones revealed the presence of a fourth tRNA gene, the gene for tRNALeu, in the cluster. The tRNALeu gene is located about 600 base pairs (bp) upstream from the tRNAAsp gene and its polarity differs from those of the other three tRNA genes. Among the repeating units, the nucleotide sequence of tRNALeu is conserved to a relatively high degree.
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Bestatin enhanced the antitumor effects of mitomycin C, 5-fluorouracil and cis-dichlorodiammineplatinum against a syngeneic solid tumor of colon adenocarcinoma 26 in BALB/c mice. The enhancement was dependent on administration schedule. Bestatin administration after treatment with the cytotoxic agents was more effective than that made before the treatment.
Tumor in the spermatic cord is infrequent. Further, among such cases, it is extremely rare to encounter a carcinoma other than a nonepithelial malignant tumor; almost all are metastatic tumors. We recently experienced an interesting case of spermatic cord tumor in a 78-year-old male. He entered our hospital with the chief complaint of a right inguinal tumor. He underwent 2 operations to excise the tumor. The extirpated tumor mass from the right spermatic cord was composed of adenocarcinoma with abundant fibrous stroma, which is considered to be metastasis from the other viscerae. We were unable to find the primary focus in spite of extensive clinical and pathological examinations. In an autopsy about four months after the 2nd operation, the tumor was confirmed to be primary intrahepatic bile duct carcinoma, which is called cholangioma. There have been only 20 cases of metastatic spermatic cord tumor reported in Japan. However, we considered that this is the 1st case caused by cholangioma in Japan and even in other countries.
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In the reproduction studies with dl-1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert.-butylamino-etha nol hydrochloride (mabuterol), a new beta 2-selective adrenoceptor stimulant, two trials were done: Segment (Seg.) I, fertility tests in male and female rats dosed before and during mating and the first week of gestation with 0.1, 2 and 40 mg/kg, and Seg. III, peri- and postnatal tests in pregnant rats dosed with 0.003, 0.01, 0.03, 0.1, 2 and 40 mg/kg from 17th day of gestation through 21st day of lactation. In Seg. III, cross-fostering was also done. The "maximum non-effective oral doses" of mabuterol from the viewpoint of parental toxicity were in Seg. I, 2 mg/kg and in Seg. III, 0.03 mg/kg, respectively. Doses above these non-effect levels were moderately toxic for the parent generation as shown by clinical signs (only at 40 mg/kg) and influence on food intake and body weight. In Seg. I, no adverse effects on fertility occurred. In Seg. III, doses of 0.1 mg/kg and above affected dose-dependently the body weight of viable pups. Additionally, 40 mg/kg decreased their perinatal survival rate.
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The antitumor effect of bestatin against syngeneic tumors such as colon adenocarcinoma 26 (colon 26) and myeloid leukemia C1498 ( C1498 ) was investigated. Bestatin effectively inhibited the growth of both tumors in vivo. The inhibition observed for colon 26 was the largest when bestatin was administered on days 1 to 5 after transplantation of the tumor. The inhibition of C1498 was the largest when bestatin was administered on days 7 to 11. In contrast to these results, bestatin was not at all inhibitory to either tumor line in vitro. Thus, the effect of bestatin administration on the functions of the spleen cells of mice bearing tumors was examined. Spleen cells taken from mice bearing colon 26 and C1498 did not neutralize the corresponding tumor. However, when bestatin was administered to these mice, spleen cells from the administered mice did neutralize the corresponding tumor. Bestatin enhanced antibody-dependent cell-mediated cytotoxicity and natural killer cell activity of the spleen cells of colon 26-bearing mice. Further, bestatin did not inhibit the growth of colon 26 in BALB/c nu/nu mice. It was concluded that bestatin exhibits its antitumor effect against colon 26 and C1498 indirectly by immunomodulation via spleen cells and possibly via T cells.